D-(-)-alpha-aminobenzylpenicillin (ampicillin) has been widely used as an antibacterial agent, especially in pediatric applications, because of its broad spectrum activity and suitability for oral administration. Administration of bacampicillin, the 1'-ethoxycarbonyloxyethyl ester of ampicillin, results in higher blood levels of ampicillin than when ampicillin itself is administered orally (see U.S. Pat. No. 3,873,521 and Bodin et al., Antimicrobial Agents and Chemotherapy, 8 (5), pp. 518-525 (1975)). The free base of bacampicillin is difficult to prepare, unstable and insoluble in water, thus rendering its oral administration impractical. The pharmaceutically acceptable acid addition salts of bacampicillin, e.g., the hydrochloride salt, are generally water-soluble. Unfortunately, such water-soluble acid addition salts possess an objectionable taste which renders the product unacceptable for pediatric use.
Conventional taste masking techniques, such as the addition of sweeteners and flavoring agents, are not capable of adequately masking the strong taste of bacampicillin acid addition salts. In one prior art technique, bacampicillin hydrochloride has been microencapsulated with a coating of ethyl cellulose and the microcapsules combined with solid vehicle ingredients in a sachet. The contents of the sachet are mixed with water to constitute a dilute single dosage suspension having a pH of about 5. Even if swallowed immediately after reconstitution, a strong bacampicillin hydrochloride taste is experienced which can be highly objectionable to an infant patient. Use of this prior art reconstituted suspension for multiple dose administration is not feasible because of the taste problem.
It is known that drugs can be microencapsulated for taste-masking purposes with a coating of a mixture of ethyl cellulose and hydroxypropyl cellulose, with the microcapsules then reconstituted as a suspension. However, the prior art does not reveal any successful application of this or any other coating procedure to the problem of preparing a stable suspension of a bacampicillin acid addition salt with palatable taste and good bioavailability.